Cyclobenzaprine

Source: Wikipedia, the free encyclopedia.
Not to be confused with
cyclosporine
.

Cyclobenzaprine
Clinical data
Trade namesFlexeril, Amrix, others
AHFS/Drugs.comMonograph
MedlinePlusa682514
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • US: ℞-only
  • In general: ℞ (Prescription only)
N-demethylation[3]
MetabolitesNorcyclobenzaprine
Elimination half-life32 hours (extended-release, range 8–37 hours),[3] 18 hours (immediate release, range 8–37 hours)[4]
ExcretionKidney
Identifiers
  • 3-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethyl-propan-1-amine
JSmol)
  • c3cc\2c(\C=C/c1c(cccc1)C/2=C/CCN(C)C)cc3
  • InChI=1S/C20H21N/c1-21(2)15-7-12-20-18-10-5-3-8-16(18)13-14-17-9-4-6-11-19(17)20/h3-6,8-14H,7,15H2,1-2H3 checkY
  • Key:JURKNVYFZMSNLP-UHFFFAOYSA-N checkY
  (verify)

Cyclobenzaprine, sold under several brand names including, historically, Flexeril, is a

musculoskeletal conditions of sudden onset.[5] It is not useful in cerebral palsy.[5] It is taken by mouth.[5]

Common side effects include

MAO inhibitor.[5] How it works is unclear.[5]

Cyclobenzaprine was approved for medical use in the United States in 1977.

generic medication.[5] In 2021, it was the 45th most commonly prescribed medication in the United States, with more than 15 million prescriptions.[6][7] It was not available in the United Kingdom as of 2012.[8]

Medical use

Cyclobenzaprine is used, in conjunction with physical therapy, to treat muscle spasms that occur because of acute musculoskeletal conditions.

muscle relaxer.[11] It is not useful for spasticity due to neurologic conditions such as cerebral palsy.[10][14]

A 2004 review found benefit for fibromyalgia symptoms, with a reported number needed to treat of 4.8 (meaning that 1 person out of every 4.8 benefits from treatment) for pain reduction, but no change in fatigue or tender points.[15] A 2009 Cochrane review found insufficient evidence to justify its use in myofascial pain syndrome.[16] It may also be used along with other treatments for tetanus.[17]

Side effects

Cyclobenzaprine results in increased rates of

muscarinic receptors.[medical citation needed
]

Agitation is a common side effect observed, especially in the elderly. Some experts[who?] believe that cyclobenzaprine should be avoided in elderly patients because it can cause confusion, delirium, and cognitive impairment.[19][20] In general, the National Committee for Quality Assurance recommends avoiding the use of cyclobenzaprine in the elderly because of the potential for more severe side effects.[21]

Dysphagia, a life-threatening side-effect, may rarely occur.[22] Treatment protocols and support should follow the same as for any structurally related tricyclic, such as tricyclic antidepressants.[23]

Overdose

The most common effects of overdose are drowsiness and

abnormal heart rhythms, severe low blood pressure, seizures, and neuroleptic malignant syndrome.[10] Life-threatening overdose is rare,[10] however, as the median lethal dose is about 338 milligrams/kilogram in mice and 425 mg/kg in rats.[10] The potential harm is increased when central nervous system depressants and antidepressants are also used; deliberate overdose often includes other drugs.[10]

Interactions

Cyclobenzaprine has major contraindications with monoamine oxidase inhibitors (MAOIs). At least one study also found increased risk of serotonin syndrome when cyclobenzaprine was taken with the serotonergic drugs duloxetine or phenelzine.[24]

These substances may interact with cyclobenzaprine:

  • Central nervous system
    major tranquilizers
    )
  • Monoamine oxidase inhibitors taken within two weeks of cyclobenzaprine may result in serious, life-threatening side effects.[10]

Cyclobenzaprine may affect the medications used in

surgical sedation and some surgeons request that patients temporarily discontinue its use prior to surgery.[25]

Pharmacology

Cyclobenzaprine is a centrally acting muscle relaxant.[26] Cyclobenzaprine is a 5-HT2 receptor antagonist; it relieves muscle spasm through action on the central nervous system at the brain stem, rather than targeting the peripheral nervous system or muscles themselves.[27]

Pharmacodynamics

Cyclobenzaprine (and metabolite)[28]
Site CBP NCBP Action
5-HT1A 5300 3200 Agonist
5-HT2A 5.2 13 Antagonist
5-HT2B 100 ??? Antagonist
5-HT2C 5.2 43 Antagonist
α1A 5.6 34 ND
α2A 4.3 6.4 Antagonist
α2B 21 150 ND
α2C 21 48 ND
H1 1.3 5.6 ND
M1 7.9 30 ND
Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.

Pharmacokinetics

Cyclobenzaprine has an oral bioavailability of about 55% and approximately 93% is bound to proteins in plasma. The half-life of the drug is 18 hours and it has a plasma clearance of 0.7 litres per minute.[26][29][30]

Comparison to other medications

Cyclobenzaprine has been found to be not inferior to tizanidine, orphenadrine, and carisoprodol in the treatment of acute lower back pain, although none have been proven to be effective for long-term use (beyond two weeks of treatment). No differences in pain or spasm scores were noted among these agents, nor when compared to benzodiazepines.[31] However, nonbenzodiazepine (including cyclobenzaprine) treatment was found to have a lower risk of medication abuse and continuation of use against medical advice.[medical citation needed] Side effects such as sedation and ataxia are also less pronounced with nonbenzodiazepine antispasmodics.[medical citation needed]

In a study on the treatment of musculoskeletal pain treatment with cyclobenzaprine alone or in combination with ibuprofen, no significant differences in pain scores were noted among the three treatment groups. Peak benefit was found to occur on day seven of the treatment for all groups.[32]

Formulations

Cyclobenzaprine 10mg tablets

By mouth, cyclobenzaprine is marketed as Apo-Cyclobenzaprin, Fexmid, Flexeril and Novo-Cycloprine. It is available in generic form. A once-a-day, extended-release formulation, Amrix, is available.[33] Cyclobenzaprine is also used by compounding pharmacies in topical creams.[citation needed]

References

  1. ^ Micromedex® 2010 – DRUGDEX Evaluations (Cyclobenzaprine Hydrochloride)
  2. ^ "Cyclobenzaprine Hydrochloride Tablets USP Revised: April 2005 Rx only". nih.gov. Retrieved 1 October 2016.
  3. ^ a b Teva Pharmaceuticals USA, Inc (May 2016). "AMR40470 (Amrix) Prescribing Information" (PDF).
  4. ^ U.S. Food and Drug Administration. "NDA 17-821/S-045 Flexeril (Cyclobenzaprine HCl) Tablets" (PDF).
  5. ^ a b c d e f g h i j "Cyclobenzaprine Monograph for Professionals". Drugs.com. AHFS. Retrieved 22 December 2018.
  6. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  7. ^ "Cyclobenzaprine - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  8. ^ "Fibromyalgia, psychiatric comorbidity, and the somatosensory cortex". British Journal of Medical Practitioners. 5 (2): a522. 2012.
  9. S2CID 8265576
    .
  10. ^ a b c d e f g h i "Cyclobenzaprine- cyclobenzaprine hydrochloride tablet, film coated". DailyMed. 30 December 2019. Retrieved 26 September 2020.
  11. ^
    PMID 15276195
    .
  12. PMID 12804507
    .
  13. ^
    PMID 11434793
    .
  14. PMID 4563483
    .
  15. PMID 14872449
    .
  16. PMID 19588406
    .
  17. ISBN 9781449689407
    .
  18. ^ "Flexeril: Side effects". RxList.com. Archived from the original on 12 September 2008. Retrieved 22 February 2010.
  19. PMID 25763449
    .
  20. ^ Potentially inappropriate medications for the elderly according to the revised Beers criteria. 2012. Duke Clinical Research Institute website. Archived 12 August 2015 at the Wayback Machine [1]
  21. ^ "High risk medications" (PDF). National Committee for Quality Assurance. Archived from the original (PDF) on 1 February 2010. Retrieved 22 February 2010.
  22. ^ "MEDICATIONS AND DYSPHAGIA/ SWALLOWING RISKS" (PDF).
  23. PMID 16846511
    .
  24. PMID 17122225
    .
  25. ^ Medical Practice of William H. Gorman, M.D. (18 February 2014). "Medications to Avoid, Continue, or Stop - Before & After Surgery". Archived from the original on 1 December 2017. Retrieved 2 February 2017.
  26. ^ a b "Cyclobenzaprine". www.drugbank.ca.
  27. PMID 8884233
    .
  28. ^ "Cyclobenzaprine (CBP) and Its Major Metabolite Norcyclobenzaprine (nCBP) Are Potent Antagonists of Human Serotonin Receptor 2a (5HT2a), Histamine Receptor H-1 and α-Adrenergic Receptors: Mechanistic and Safety Implications for Treating Fibromyalgia Syndrome by Improving Sleep Quality". ACR Meeting Abstracts. Retrieved 27 January 2022.
  29. ^ "Cyclobenzaprine". pubchem.ncbi.nlm.nih.gov.
  30. S2CID 7749001
    .
  31. ^ "Medscape: Medscape Access". medscape.com. Retrieved 1 October 2016.
  32. doi:10.1016/j.annemergmed.2004.07.286
    .
  33. ^ "Patient Web site for Amrix (Cyclobenzaprine Hydrochloride Extended-Release Capsules)". amrix.com. Retrieved 1 October 2016.

External links

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